Recombinant adenoviral vectors are widely applied for gene therapy applications and vaccines. To date, 51 different adenovirus serotypes have been identified. The subgroup C adenoviruses have been most extensively studied for applications such as gene therapy; especially serotype 2 and 5 (Ad2 and Ad5) are widely used in the art. Recombinant Ad5 is used in a variety of different purposes, including vaccination. Importantly, Ad5 vector-based vaccines have been shown to elicit potent and protective immune responses in a variety of animal models. Moreover, large-scale clinical trials for HIV vaccination are ongoing in which Ad5-based recombinant vectors are being used (WO 01/02607; WO 02/22080; Shiver et al. 2002; Letvin et al. 2002; Shiver and Emini. 2004). However, the utility of recombinant Ad5 vector-based vaccines for HIV and other pathogens will likely be significantly limited by the high seroprevalence of Ad5-specific neutralizing antibodies (NAbs) in human populations. The existence of anti-Ad5 immunity has been shown to suppress substantially the immunogenicity of Ad5-based vaccines in studies in mice and rhesus monkeys. Early data from phase-1 clinical trials show that this problem may also occur in humans (Shiver 2004).
One promising strategy to circumvent the existence of pre-existing immunity in individuals previously infected with the most common human adenoviruses (such as Ad5), involves the development of recombinant vectors from adenovirus serotypes that do not encounter such pre-existing immunities. Human adenoviral vectors that were identified to be particularly useful are based on serotypes 11, 26, 34, 35, 48, 49, and 50 as was shown in WO 00/70071, WO 02/40665 and WO 2004/037294 (see also Vogels et al. 2003). Others have found that also adenovirus 24 (Ad24) is of particular interest as it is shown to be a rare serotype (WO 2004/083418).
A similar strategy is based on the use of simian adenoviruses since these do typically not infect humans. They exhibit a low seroprevalence in human samples. They are however applicable for human use since it was shown that these viruses could infect human cells in vitro (WO 03/000283; WO 2004/037189).
It was shown that adenovirus serotype 35 (Ad35) vector-based vaccines could elicit potent cellular immune responses that were not significantly suppressed by anti-Ad5 immunity (Barouch et al. 2004; Vogels et al. 2003). Similarly, chimpanzee adenoviruses have been shown to elicit immune responses that were minimally affected by anti-Ad5 immunity (Farina et al. 2001; Pinto et al. 2003). It was recently demonstrated that neutralizing antibodies (NAbs) and CD8+ T lymphocyte responses both contribute to anti-Ad5 immunity, whereas Ad5-specific NAbs appear to play the primary role (Sumida et al. 2004). Although this development appears to be a very useful approach, it was also demonstrated in mice that Ad35 vector-based vaccines proved less immunogenic than Ad5 vector-based vaccines in studies in which there was no pre-existing Ad5-immunity (Barouch et al. 2004).
Clearly, there is a need in the field for alternative adenoviral vectors that do not encounter pre-existing immunities in the host, but that are still immunogenic and capable of inducing strong immune responses against the proteins encoded by the heterologous nucleic acids inserted in the nucleic acid carried by the vector.